Caveolin-1 Controls Hyperresponsiveness to Mechanical Stimuli and Fibrogenesis-Associated RUNX2 Activation in Keloid Fibroblasts

Chao Kai Hsu, Hsi Hui Lin, Hans I. Harn, Rei Ogawa, Yang Kao Wang, Yen Ting Ho, Wan Rung Chen, Yi Chao Lee, Julia Yu Yun Lee, Shyh Jou Shieh, Chao Min Cheng, John A. McGrath, Ming Jer Tang

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15 Citations (Scopus)

Abstract

Keloids are pathological scars characterized by excessive extracellular matrix production that are prone to form in body sites with increased skin tension. CAV1, the principal coat protein of caveolae, has been associated with the regulation of cell mechanics, including cell softening and loss of stiffness sensing ability in NIH3T3 fibroblasts. Although CAV1 is present in low amounts in keloid fibroblasts (KFs), the causal association between CAV1 down-regulation and its aberrant responses to mechanical stimuli remain unclear. In this study, atomic force microscopy showed that KFs were softer than normal fibroblasts with a loss of stiffness sensing. The decrease of CAV1 contributed to the hyperactivation of fibrogenesis-associated RUNX2, a transcription factor germane to osteogenesis/chondrogenesis, and increased migratory ability in KFs. Treatment of KFs with trichostatin A, which increased the acetylation level of histone H3, increased CAV1 and decreased RUNX2 and fibronectin. Trichostatin A treatment also resulted in cell stiffening and decreased migratory ability in KFs. Collectively, these results suggest a role for CAV1 down-regulation in linking the aberrant responsiveness to mechanical stimulation and extracellular matrix accumulation with the progression of keloids, findings that may lead to new developments in the prevention and treatment of keloid scarring.

Original languageEnglish
Pages (from-to)208-218
Number of pages11
JournalJournal of Investigative Dermatology
Volume138
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Hsu, C. K., Lin, H. H., Harn, H. I., Ogawa, R., Wang, Y. K., Ho, Y. T., Chen, W. R., Lee, Y. C., Lee, J. Y. Y., Shieh, S. J., Cheng, C. M., McGrath, J. A., & Tang, M. J. (2018). Caveolin-1 Controls Hyperresponsiveness to Mechanical Stimuli and Fibrogenesis-Associated RUNX2 Activation in Keloid Fibroblasts. Journal of Investigative Dermatology, 138(1), 208-218. https://doi.org/10.1016/j.jid.2017.05.041